The somatomedins (SM) are a family of growth hormone-dependent, insulin-like peptides, with anabolic and mitogenic actions for a wide variety of cell lines. The insulin-like effects of SM are believed to be mediated via the insulin receptor, while the growth-promoting action of SM is presumably mediated via a distinct cell membrane receptor. The goal of this project is to correlate specific binding of SM to cell receptors with in vitro biological actions, and to apply these observations to the investigation of clinical disorders of growth. Tissue receptors for SM-C/IGF-I and for IGF-II will be characterized on the following cell lines: peripheral circulating mononuclear cells, cultured IM-9 lymphocytes, cultured human and chick fibroblasts and chondrocytes, and human adipocytes. Hormonal control of the number and affinity of SM receptor sites by the various somatomedin peptides, insulin and growth hormone, will be evaluated under both in vitro and in vivo conditions. Binding of SM to cell receptors will be correlated with biological effects, such as amino acid and glucose transport, sulfation and leucine incorporation, thymidine incorporation, and stimulation of cell multiplication. The development of these methodologies will permit a comprehensive study of multiple facets of growth, including measures of immunoassayable and receptor active hGH and SM-C, quantification of SM-C receptor sites, and evaluation of in vitro tissue responsiveness to SM. These data will be applied to the evaluation of specific normal and abnormal growth states, such as growth hormone deficiency and acromegaly, osteochondrodysplasias, Turner Syndrome, growth retardation associated with diabetes mellitus and chronic renal failure, and the aging process.